African Americans (AAs) currently experience an inequitable burden of adverse HIV-related outcomes in the United States (U.S.). Such adverse outcomes include infection, AIDS diagnoses, virologic failure, and death. One of the three goals of the National HIV/AIDS Strategy for the U.S. issued by the White House in 2010 was to permanently reduce long-standing health disparities in HIV-disease, in particular racial/ethnic disparities. Identifying the major pathways that mediate HIV racial/ethnic disparities is critical or prioritizing targets for effective interventions to achieve this goal. Differential use (i.e., initation, modification, and adherence) of antiretroviral therapies (ARTs) by race may be a main mediator of observed racial disparities in adverse HIV- related outcomes between AAs and Caucasians in the U.S. However, short-term interventions (e.g., education programs) solely and directly targeted at improving ART initiation and adherence among AAs who have been observed to receive and adhere to ART less often than Caucasians may be insufficient to permanently reduce racial differences in adverse HIV-related outcomes. Therefore, to meet the goals of the National HIV/AIDS Strategy, more upstream, distal factors potentially influenced by race that likely directly or indirectly effect ART use and in turn HIV-related outcomes should be evaluated as important mediators of HIV racial disparities. As such, the goal of the proposed research is to establish whether inadequate insurance and food insecurity are important, more distal mediators through which a substantial proportion of differences in virologic response between HIV-infected AA and Caucasian adults in the U.S. operate. Existing and to be collected data from AA and Caucasian participants enrolled in the large, racially and geographically diverse Center for AIDS Research Network of Integrated Clinical Systems (CNICS) combined HIV clinic cohort (R24 AI067039; M. Saag, PI; www.uab.edu/cnics/) will be used for the proposed study. Specifically, this study aims to (1) examine if and quantify the degree to which food insecurity mediates racial differences in HIV clinic attendance, (2) examine if and quantify the degree to which inadequate insurance and food insecurity mediate racial differences in virologic response, and (3) examine if and quantify the degree to which HIV clinic attendance mediates differences in virologic response by food insecurity. Novel quantitative methods for causal mediation analysis based on the counterfactual framework will be used to estimate total, direct, and indirect effects and in turn the relevant proportion mediated for all proposed mediation analyses. We expect that completing the proposed aims will establish whether food insecurity and inadequate insurance represent important, more distal mediators of HIV racial disparities that should be prioritized as targets when developing effective interventions to achieve the health disparities goals of the 2010 U.S. National HIV/AIDS Strategy.